The NHLBI Division of Cardiovascular Diseases 2008 strategic plan has highlighted the need to identify strategies to halt the atrial fibrillation (AF) epidemic and reduce its related morbidity. AF is projected to afflict up to 16 million individuals by the year 2050, costing over $6.7 billion annually. AF is not currently explained by known risk factors, underscoring the need to identify novel triggers. Sleep-disordered breathing (SDB) is common in patients with cardiovascular disease and its attendant hypoxemia and autonomic dysfunction likely enhance AF propensity. Thus, SDB may represent a novel target for AF prevention and treatment strategies. A key, unanswered question is whether the association of SDB to AF is independent of structural heart disease, or merely a marker for cardiac dysfunction. Although our prior cross-sectional work has shown a 2-4 fold higher odds of AF related to SDB, these and other reports have not included cardiac structural data or autonomic or biochemical measures, and have addressed only arrhythmic events occurring during an overnight sleep study. In this application, we will examine paroxysmal AF (PAF), an early stage risk factor for persistent AF, and relevant to this application because it occurs prior to extensive cardiac electrical remodeling and fibrosis. PAF provides an ideal setting to investigate the immediate influences of SDB and examine temporal patterns given its intermittent nature. We will perform a case control study of 150 patients with PAF (from our local AF clinic) matched to 150 patients without PAF (from local cardiology and internal medicine clinics). Each group will be matched on important confounders such as age (15 years), gender, race and coronary heart disease, and characterized using detailed collection of overnight sleep study data, echocardiographic measures, biomarkers and 1-week continuous ECG monitoring. Data will be collected in order to: clarify the extent that respiratory event frequency, apnea subtype (obstructive versus central), and hypoxia are associated with PAF independent of cardiac structural abnormalities;explore the extent to which cardiac morphology, pathways of inflammation, oxidative stress and autonomic dysfunction mediate the SDB-PAF relationship and identify whether temporal patterns of AF paroxysms differ in patients with SDB. PUBLIC HEALTH RELEVANCE: Data generated from this application will be key for developing new strategies to reduce atrial fibrillation (AF)-related morbidity including stroke, heart failure and also death by providing a basis to incorporate sleep disordered breathing (SDB) identification and treatment in AF clinical pathways for prevention. Expected results will be of high impact given ability to identify and inform future screening and treatment approaches for prevention and/or management of AF and identify key outcomes for future studies and clinical trials.